Osteonecrosis, including avascular necrosis, is a relatively common disorder that has been associated with a wide range of conditions, affecting patients with a variety of risk factors. The majority of cases are secondary to trauma. However, for non-traumatic cases, there often remains a diagnostic challenge in defining the cause of bone death. Non-traumatic osteonecrosis has been associated with corticosteroid usage, alcoholism, infections, hyperbaric events, storage disorders, marrow infiltrating diseases, coagulation defects, and some autoimmune diseases. However, a large number of idiopathic cases of osteonecrosis have been described without an obvious associated risk factor. (Assouline-Dayan et al., Semin. Arthritis Rheum. 32(2):94-124 (2002)).
Avascular necrosis of the femoral head (ANFH) is a debilitating disease that usually leads to destruction of the hip joint in the third to fifth decade of life. The disease prevalence is unknown, but it has been estimated that 10,000-20,000 new cases per year are diagnosed in the United States. (Mankin, N. Engl. J. Med. 326:1473-1479 (1992); Mont et al., J. Bone Joint Surg. Am., 77:459-474 (1995)) Nearly half the patients with ANF require hip replacement before 40 years of age. Despite continued improvement in the design and technique of hip arthroplasty, the durability of total hip arthroplasty in young and active patients remains poor. Furthermore, the failure rate of arthroplasties is around 30%, after an average of 10 years follow-up. (Duffy et al., J. Arthroplasty, 16:140-144 (2001))
It has been suggested that a common pathogenesis pathway of ANFH involves the interruption of blood circulation to the antero-lateral part of the femoral head, leading to ischemic insult and bone collapse. The disease is aggravated by mechanical disruption (e.g., trauma, hip fracture), external pressure on or damage to a vessel wall (e.g., vasculitis, radiation therapy, systemic lupus erythematosus), arterial thrombosis or embolism (e.g., sickle cell disease, corticosteroid use, alcohol abuse) and venous or blood outflow occlusion (e.g., infection). Cases of ANFH that were initially considered idiopathic have been associated with heritable thrombophilia (an increased tendency for intravascular thrombosis) or hyperfibrinolysis (a reduced ability to lyse thrombi). (Glueck et al., Clin. Orthop., 43-56 (1997); Glueck et al., Clin. Orthop, 19-33 (2001); Jones et al., J. Rheumatol. 30:783 (2003)). Although many ANFH cases are associated with known underlying risk factors and classified as secondary ANFH, 15-30% of patients showing no apparent risk factors are classified as primary or idiopathic avascular necrosis of the femoral head (idiopathic ANFH). (Assouline-Dayan et al., Semin. Arthritis Rheum. 32:94-124 (2002)).
Accordingly, early detection of osteonecrosis is important for surgical and other medical treatment options because a patient's prognosis may depend on the stage and location of the lesion. If the development of osteonecrosis can be detected early, corrective surgery or alternative therapy can be effectively carried out with more successful prognosis. Further, the development of additional treatment options for subjects with ANFH or osteonecrosis is desirable, including gene therapy and cell therapy approaches.